A reducing environment stabilizes HIF-2alpha in SH-SY5Y cells under hypoxic conditions.
Accumulating evidence suggests that hypoxia-inducible factor-2 (HIF-2) is important for the cellular response to hypoxia. However, it is not clear how HIF-2 is regulated under hypoxic conditions. We investigated kinetic changes in redox status and HIF-2alpha accumulation in hypoxic SH-SY5Y cells. Our results demonstrated that hypoxia caused a reducing environment and increased HIF-2alpha protein levels. Experiments with redox modulations (N-acetylcysteine and l-buthionine sulfoximine) confirmed that a reducing environment induced HIF-2alpha accumulation while an oxidizing environment decreased it. In addition, experiments with SOD mimic, catalase, and exogenous H2O2 provided evidence that the presence of H2O2 down-regulated the amount of HIF-2alpha protein. This study offers novel evidence supporting redox status regulation of HIF-2alpha accumulation under hypoxic conditions.
Chen
Hu
H
College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Shi
Honglian
H
D000111:Acetylcysteine / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D000072105:Superoxide Dismutase-1; D000099162:Endothelial PAS Domain-Containing Protein 1
D000111:Acetylcysteine; D051792:Basic Helix-Loop-Helix Proteins; D019328:Buthionine Sulfoximine; D002374:Catalase; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099162:Endothelial PAS Domain-Containing Protein 1; C000606290:SOD1 protein, human